Announcements:• I got caught checking my cell phone, so in

order to avoid being labelled a hypocrite, you can text in class, just give me your attention when I lecture!

• No one wants to go to office hours on a Friday afternoon should I change my hours?

• Quiz 3 average: 83%

• Send me emails if you want help on anything but can’t attend office hours, if you’re still having trouble with the first weeks material, it isn’t going to get easier…

22

From strings to blobs

From strings to blobs

How? Why?

From there to here• Week 3: How DNA can ‘mean’

anything; how it can pass that meaning on (replication)

• Week 4: How DNA can send out a ‘message’ (transcription); how that ‘message’ can be ‘translated’ into amino acids

• Now: How a string of amino acids is formed into a functional shape

3

What matters today?• How do we go from the ‘ticker tape’ of an mRNA to a

machine?

• machine = 3D object that does stuff

• Who shapes proteins into their shapes? Terminology: ‘folding’

• How specific amino acids and protein shapes give rise to operational machines that perform body tasks

4

Meet the building blocks

• There are only about 5 ways molecular surfaces can be

• What are they?

• Amino acid easter egg hunt--find the one(s) that...

5

How does it feel? 6

7

http://upload.wikimedia.org/wikipedia/commons/a/a9/Amino_Acids.svg

Ooey gooey rich & chewy inside...

• Protein folding, oil not mixing with water, and membrane formation all reflect the same principle

• In protein folding, the constraint is that the individual units are all attached to a pair of neighbors

• Many proteins need no further ‘instruction’ than their sequence & water to correctly assume their superhero identity

8

If THIS is true…•Pencils made of….

http://www.nano-enhanced-wholesale-technologies.com/faq/

carbon-forms.htm

If THIS is true…

•Pencils made of….

•Paper made of…

Question Authority

To your pencils, index cards & oil-water mixes!

• Color one face of an index card with pencil

• Cut out circles with hole puncher

• Predict: what will happen?

• Drop into oil/water bottles; mix

11

12

Your turnYou ‘fold’ a protein: ProFolder (Bio181L_Go)

Show me each solution (Q. 3)Leave the 2nd one on screen

Profolder features• Destinations (lower right) => Folding

• Top: amino acid string

• Squares: places amino acids could go. Note ‘Undo last’ button

• Two spots--use one to improve upon what you did in the other

• Bottom: note that when you mouseOver an amino acid, it’s structure & ‘feel’ are shown

13

14How does yours compare? 14

15Other ‘rules’ of folding

(+)

(-)

Images of 3D16

Q. 4

1717

Life’s blood:

Hemoglobin

Life’s blood:

Hemoglobin

How? Why?

Hemoglobin: overview 18

http://www.youtube.com/watch?v=WXOBJEXxNEo&feature=related

19Scale & role

Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease

Small capillary(blood vessel)

Tetramer:4 protein chains

(~145 amino acids)

Oxygen molecule2 atoms

Heme:C34H32O4N4Fe

201-2-3-4 protein!

http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

21Hemoglobin: what is it?

Image source: http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.html

What you’ll learn today• How hemoglobin’s amino acid sequence

generates its structure

• Why hemoglobin is a tetramer (gang of four)

22

Todays assignments30% Worksheet: easter egg hunt

60% points hemoglobin tutorial

10% points hemoglobin mini-research

23

24

Karl

Jillian

Alice

Blake

Adam

Anders

Montez

Hemoglobin_intro• Turn OFF Wi-Fi; QUIT safari (not close window)

• Read...

• the instructions on each question...

• the instructions on the webpage...

• all the words of each question...

• Ask yourself: will you be the monkeys at the typewriter, or Shakespeare?

• CLOSE EACH PAGE WHEN YOU’RE DONE WITH IT!

25

2626

On the relative likelihood of accidents...

On the relative likelihood of accidents...

What specifically would it take for...

• A lysine to become a glycine?

• To your codon tables! (page 4-8 in lab manual)

• How often is that going to happen?

27

More on your disease!

• Get into your Genetic Disease groups

• Write up Part 2 of the assignment (view link on course homepage)

• FOLLOW THE RUBRIC

• Do you remember what disease you have? You should’ve written it down… If not, ask me.

• EMAIL ME YOUR ANSWERS: jcumsky@email.arizona.edu

• Provide your Genetic Disease Name in Subject

28

2929

HomeworkHomework